Tetrahydropyridine-(or 4-hydroxypiperidine) alkylazoles

ABSTRACT

The present invention relates to the compounds of general formula &lt;IMAGE&gt; (1)  used as medicaments possessing therapeutic activity for the treatment of anxiety, psychosis, epilepsy, convulsion, motoricity problems, amnesia, cerebrovascular diseases or senile dementia.

The present invention relates to new 4-aryltetra-hydropyridines and4-arylpiperidinols linked to alkyl-azoles of general formula (I)##STR2## and to their physiologically acceptable salts, to the processesfor their preparation, to their application as medicaments and to thepharmaceutical compositions which contain them.

The compounds which are the subjects of the invention can also be usedin the pharmaceutical industry as intermediates and for the preparationof medicaments.

These compounds possess a powerful affinity for sigma and/or 5-HT_(1A)receptors and are therefore potentially useful in the treatment ofcertain psychic and neurological disorders of human beings and othermeals.

Phenomena exist which involve sigma receptors in the treatment ofpsychosis. Many atypical antipsychotics, such as rimcazole (Schwarcz, G.et al., Drug Dev. Res., 1985, 5, 387), remoxipride (Wadworth, A. N. etal., Drugs 1990, 40, 863) or thiospirone (Jain, A. K. et al., Int. Clin.Psychopharmacol. 1987, 2, 129), show a significant affinity for sigmareceptors.

Moreover, studies of the biology and function of sigma receptorsindicate that ligands for the sigma receptor can be effective in thetreatment of certain motor disorders, in particular Huntington's chorea,dystonia and Tourette's syndrome. The presence of sigma receptors in thesubstantia nigra makes it possible to use them in the treatment ofParkinson's disease (Walker, J. M. et al., Pharmacological Reviews,1990, 42, 355).

Certain ligands for sigma receptors are involved in the modulation ofthe effects produced by the intervention of the NMDA receptor and act asantiischemic agents in in vivo tests (Rao, T. S. et al., MolecularPharmacology, 1990, 37, 978), with the possibility of use asneuroprotectors and in the treatment of epilepsy and of convulsion(Kaiser C., Neurotransmissions VII, 1991).

It has been said that ligands for sigma receptors exhibit antiamnesiceffects in animal models (Early et al., Brain Research, 1991, 546, 281).

Sigma ligands influence the levels of acetylcholine in animal models(Matsuno et al., Brain Research 1992, 575, 315) and can consequently beused in the treatment of senile dementia, for example of Alzheimer type.

Ligands for 5-HT_(1A) receptors, in particular agonists or partialagonists for 5-HT_(1A), show a proven anxiolytic and antidepressantactivity (Glitz, D. A., Drugs, 1991, 41, 11).

Consequently, agents having a powerful affinity for sigma and/or5-HT_(1A) receptors can be used in one or a number of the treatmentsindicated.

Examples of 4-aryl-1,2,3,6-tetrahydropyridines and of4-aryl-4-hydroxypiperidines are found in the bibliography; however,compounds in which these sub-structures are joined to the nitrogen of anazole ring by means of an unsubstituted alkyl chain are not found to bedescribed:

Davis L. Temple et al., U.S. Pat. No. 4,320,131; 16 Mar. 1982.

Richard A. Glennon et al., J. Med. Chem., 1991, 34, 3360-65.

Jean-Luc Malleron et al., J. Med. Chem., 1991, 34; 8, 2477-83.

Henning Bottcher et al., J. Med. Chem., 1992, 35, 4020-26.

Zhuihua Sui et al., Synthesis,. 1993, 803-8.

David I. Schuster et al., J. Med. Chem., 1993, 36, 3923-28.

David J. Wustrow et al., BioMed. Chem. Lett., 1993, 3, 277-80.

Shimazaki Norihiko et al., Can. Pat. App., CA 2053475AA.

The Inventors have previously described a series of N-alkylazoles joinedto the nitrogen of various heterocycles which are useful asnon-benzodiazepine agents in the treatment of anxiety (European PatentsNo. EP 382637, EP 497659 and EP 502786) and in the treatment of otherbehavioral disorders (European Patents EP 429360 and EP 497658).Descriptions are given in the cited patents of the compounds of generalformula (I) in which A represents, in all cases, a nitrogen atom and itconsequently concerns a piperazine ring. In the present invention, thepiperazine ring is replaced by a piperidine or a tetrahydropyridine.

The compounds which are the subjects of the invention correspond to thegeneral formula (I) ##STR3## in which R₁, R₂ and R₃, which are identicalor different, each represent a hydrogen atom, a halogen atom, a linearor branched alkyl radical, an aryl or substituted aryl radical or analkoxyl radical. Moreover, two adjacent radicals can form a saturated oraromatic ring.

A represents a carbon atom and the dotted line represents an additionalbond or else A represents a carbon atom bonded to a hydroxyl group(C--OH) and the dotted line represents the absence of an additionalbond.

n can have values ranging from 2 to 6

Z₁ represents a nitrogen atom or a substituted carbon atom which can berepresented by C--R₄

Z₂ represents a nitrogen atom or a substituted carbon atom which can berepresented by C--R₅

Z₄ represents a nitrogen atom or a substituted carbon atom which can berepresented by C--R₇

R₄, R₅, R₆ and R₇, which are identical or different, represent ahydrogen atom, a halogen atom, a linear or branched alkyl radical, ahydroxyl radical, an alkoxyl radical, a carboxyl radical, a carboxamideradical, an alkyl carboxylate radical or an aryl or substituted arylradical or else two adjacent radicals can form part of another ring,which may or may not be aromatic.

The invention also relates to the physiologically acceptable salts ofthe compounds of general formula (I), in particular the salts ofhydrochloric, hydrobromic, sulfuric, phosphoric, acetic, lactic,malonic, succinic, glutaric, fumaric, malic, tartaric, citric, ascorbic,maleic, benzoic, phenylacetic, cinnamic and salicylic acids and ofalkane-, cycloalkane- or arenesulfonic acids.

The new derivatives of general formula (I) can be prepared according tothe following processes:

Process A

By reaction of a spiran derivative of general formula (II) ##STR4## inwhich R₁, R₂, R₃ and A have the meaning indicated above, m can havevalues ranging from 0 to 4 and X represents a leaving group, such aschloro, bromo, mesyloxy or tosyloxy,

with a nitrogenous heterocycle of general formula (III) ##STR5## inwhich Z₁, Z₂, Z₄ and R₆ have the meaning indicated above.

The reaction is carried out in a solution of dimethyl sulfoxide,dimethylformamide, an alcohol such as ethanol, an aromatic hydrocarbonsuch as toluene or an aliphatic hydrocarbon such as hexane or an ethersuch as dioxane. This reaction is preferably carried out in the presenceof a base such as potassium carbonate or triethylamine.

The reaction temperature varies between room temperature and the refluxtemperature of the solvent used.

The reaction times vary between 1 and 24 hours.

Process B

By simultaneous "one pot" reaction between a derivative of generalformula (IV), an alkylating agent of general formula (V) and anitrogenous heterocycle of general formula (III). ##STR6## where

R₁, R₂, R₃, A, X, n, Z₁, Z₂, Z₄ and R₆ have the meaning given above.

The reaction is carried out in a solution of dimethyl sulfoxide,dimethylformamide, an alcohol such as ethanol, an aromatic hydrocarbonsuch as toluene or an aliphatic hydrocarbon such as hexane or an ethersuch as dioxane. This reaction is preferably carried out in the presenceof a base such as potassium carbonate or triethylamine.

The reaction temperature varies between room temperature and the refluxtemperature of the solvent used.

The reaction times vary between 1 and 24 hours.

Process C

The preparation of the compounds of general formula (I) can be carriedout by reaction, under alkylation conditions, of the amines of generalformula (IV) ##STR7## in which R₁, R₂, R₃ and A have the meaning givenabove, with compounds of general formula (VI) ##STR8## in which X, n,Z₁, Z₂, Z₄ and R₆ have the meaning indicated above.

The reaction is carried out in a solution of dimethyl sulfoxide,dimethylformamide, an alcohol such as ethanol, an aromatic hydrocarbonsuch as toluene or an aliphatic hydrocarbon such as hexane or an ethersuch as dioxane. This reaction is preferably carried out in the presenceof a base such as potassium carbonate or triethylamine.

The reaction temperature varies between room temperature and the refluxtemperature of the solvent used.

The reaction times vary between 1 and 24 hours.

Process D

The compounds of general formula (I) can be prepared by reaction, underalkylation conditions, of a compound of general formula (VII) ##STR9##in which

R₁, R₂, R₃, n and A have the meaning indicated above with a nitrogenousheterocycle of general formula (III) ##STR10## in which Z₁, Z₂, Z₄ andR₆ have the meaning given above.

The reaction is carried out in a solution of dimethyl sulfoxide,dimethylformamide, an alcohol such as ethanol, an aromatic hydrocarbonsuch as toluene or an aliphatic hydrocarbon such as hexane or an ethersuch as dioxane. This reaction is preferably carried out in the presenceof a base such as potassium carbonate or triethylamine.

The reaction temperature varies between room temperature and the refluxtemperature of the solvent used.

The reaction times vary between 1 and 24 hours.

Process E

By dehydration of compounds of general formula (I) ##STR11## in whichR₁, R₂, R₃, n, Z₁, Z₂, Z₄ and R₆ have the meaning indicated above, Arepresents a carbon atom linked to a hydroxyl group (C--OH) and thedotted line represents the absence of any additional bond.

The reaction is carried out in acid medium, such as, for example,hydrochloric acid, trifluoroacetic acid, sulfuric acid or phosphoricacid, or by treatment with thionyl chloride in benzene.

The reaction temperature varies between room temperature and 180° C.

The reaction times vary between 1 and 14 hours.

Process F

By addition of organometallic reagents, for example phenyllithium orphenylmagnesium bromide, to compounds of general formula (VIII)##STR12## in which n, Z₁, Z₂, Z₄ and R₆ have the meaning given above.

The reaction is carried out in a solution of an inert solvent, generallyan ether such as, for example, dimethoxyethane, tetrahydrofuran or ethylether.

The reaction temperature varies between room temperature and the refluxtemperature of the solvent used.

The reaction times vary between 5 minutes and 24 hours.

Process G

By reduction of the carbonyl of the amide group of compounds of generalformula (IX) ##STR13## in which

R₁, R₂, R₃, A, n, Z₁, Z₂, Z₄ and R₆ have the meaning indicated above.

The reaction is preferably carried out in an inert organic solvent, suchas ethyl ether or tetrahydrofuran, with reducing agents such as LiAlH₄,AlH₃ or diborane.

The reaction temperature varies between room temperature and the refluxtemperature of the solvent used.

The reaction times vary between 5 minutes and 24 hours.

Process H

The corresponding salt is obtained by reaction of a compound of generalformula (I) with a nontoxic inorganic or organic acid in a suitablesolvent, which can be, for example, an alcohol such as methanol, ethanolor any one of the propanols or butanols, an ester such as ethyl acetateor a nitrile such as acetonitrile, and by using conventional techniquesfor precipitation, crystallization, and the like.

The inorganic acid is chosen, inter alia, from hydrochloric,hydrobromic, sulfuric and phosphoric acids and the organic acid ischosen from mono-, di- or tricarboxylic acids, such as, for example,acetic, lactic, malonic, succinic, glutaric, fumaric, malic, tartaric,citric, ascorbic, maleic, benzoic, phenylacetic, cinnamic and salicylicacids, and alkane-, cycloalkane- or arenesulfonic acids.

The mono- or disalts of the acid can be formed and these salts can be inthe anhydrous or hydrated form.

The invention is made clearer by the following examples, given simply byway of information, it being understood that they can in no way limitthe specific conditions of the process nor the scope of the invention.

PROCESS A EXAMPLE 1

Preparation of 4-chloro-1-4-(4-hydroxy-4-phenyl-1-piperidyl)butyl!-1H-pyrazole.

A mixture of 15.0 g (48 mmol) of 8-hydroxy-8-phenyl-5-azoniaspiro4,5!decane, 5.4 g (53 mmol) of 4-chloropyrazole and 13.2 g of potassiumcarbonate in 200 ml of dimethylformamide is heated at reflux for 20hours. Evaporation to dryness is then carried out at reduced pressure,the residue is redissolved in chloroform and washing is carried outrepeatedly with water. The organic phase is dried with anhydrous sodiumsulfate and evaporation is carried out at reduced pressure, a crudeproduct being obtained which is suspended in ethyl ether, which isfiltered while cold and which is washed with ethyl ether. 12.4 g (37.1mmol) of 4-chloro-1-4-(4-hydroxy-4-phenyl-1-piperidyl)butyl!-1H-pyrazole are obtained.

The melting point and the spectroscopic data for the identification ofthis product are provided in Table I.

PROCESS B EXAMPLE 7

Preparation of 4-chloro-1- 4-4-hydroxy-4-(3-trifluoromethylphenyl)-1-piperidyl!butyl!-1H-pyrazole.

A mixture of 8.6 g (35 mmol) of4-hydroxy-4-(3-trifluoromethylphenyl)-1-piperidine, 7.68 g of1,4-di-bromobutane and 13.8 g of potassium carbonate in 100 ml ofdimethylformamide is heated at reflux for 4 hours. 3.59 g (35 mmol) of4-chloropyrazole are then added and the reaction mixture is maintainedat reflux for 14 hours. Evaporation to dryness is then carried out atreduced pressure, the residue is redissolved in chloroform and washingis carried out repeatedly with water. The organic phase is dried withanhydrous sodium sulfate and evaporated at reduced pressure, a crudeproduct being obtained which is purified by chromatography on silicagel. 9.7 g (24.2 mmol) of 4-chloro-1-{4-4-hydroxy-4-(3-trifluoromethylphenyl)-1-piperidyl!butyl}-1H-pyrazole areobtained.

The spectroscopic data for the identification of this product are foundin Table I.

PROCESS C EXAMPLE 14a

Preparation of 1- 4-(4-phenyl-1,2,3,6-tetrahydro-1-pyridyl)butyl!indole.

A mixture of 4.8 g (30 mmol) of 4-phenyl-1,2,3,6-tetrahydropyridine,6.22 g of 1-(4-chlorobutyl)indole and 8.3 g of potassium carbonate in100 ml of dimethylformamide is heated at 90° C. for 3 hours. Evaporationto dryness is then carried out at reduced pressure, the residue isredissolved in chloroform and washing is carried out repeatedly withwater. The organic phase is dried with anhydrous sodium sulfate andevaporation is carried out at reduced pressure, a crude product beingobtained which is purified by chromatography on silica gel. 5.7 g (17.3mmol). of 1- 4-(4-phenyl-1,2,3,6-tetrahydro-1-pyridyl)butyl!indole areobtained.

The spectroscopic data for the identification of this product are foundin Table II.

PROCESS D EXAMPLE 21a

Preparation of 4-chloro-1-3-(4-phenyl-1,2,3,6-tetrahydro-1-pyridyl)propyl!-1H-pyrazole.

A solution of 2.05 g (20 mmol of 4-chloropyrazole in dimethylformamideis added dropwise to a suspension of 1.0 g of NaH in dimethylformamide.The white suspension is heated for 30 minutes at 100° C. Cooling iscarried out and 4.7 g (20 mmol) of1-(3-chloropropyl)-4-phenyl-1,2,3,6-tetrahydropyridine, dissolved indimethylformamide, are added. Heating is carried out at reflux for 2hours. Evaporation to dryness is then carried out and the residue isextracted with chloroform, washed with water and dried with sodiumsulfate. The resulting crude product is purified by chromatography onsilica gel. 5.2 g (17.2 mmol) of 4-chloro-1-3-(4-phenyl-1,2,3,6-tetrahydro-1-pyridyl)propyl!-1H-pyrazole areobtained.

The spectroscopic data for the identification of this product areprovided in Table II.

PROCESS E EXAMPLE 2a

Preparation of 1-4-(4-phenyl-1,2,3,6-tetrahydro-1-pyridyl)butyl!-1H-benzimidazole.

A solution of 13.4 g (38.2 mmol) of 1-4-(4-hydroxy-4-phenyl-1-piperidyl)butyl!-1H-benzimidazole, 150 ml ofconcentrated HCl and 75 ml of ethanol is heated at reflux for 6 hours.The ethanol is then evaporated and the aqueous solution is cooled,basified with dilute NaOH and extracted with chloroform. The organicphase is dried with anhydrous sodium sulfate and evaporated at reducedpressure, a crude product being obtained which is purified bychromatography on silica gel. 9.1 g (27.5 mmol) of 1-4-(4-phenyl-1,2,3,6-tetrahydro-1-pyridyl)butyl!-1H-benzimidazole areobtained.

The melting point and the spectroscopic data for the identification ofthis product are provided in Table II.

PROCESS F Example 11

Preparation of 4,5-dichloro-1-{4-4-hydroxy-4-(4-methylphenyl)-1-piperidyl!butyl}-2-methyl-1H-imidazole.

A solution of 1.0 g (3.3 mmol) of 4,5-dichloro-2-methyl-1-4-(4-oxo-1-piperidyl)butyl!-1H-imidazole in 10 ml of anhydroustetrahydrofuran is added to a suspension of 1.08 g (11.4 mmol) of MgCl₂in 15 ml of anhydrous THF at -40° C. and under a nitrogen atmosphere.The mixture is stirred for 5 minutes and then, at -40° C., 6.8 ml of a1.0M solution of 4-methylphenylmagnesium bromide are added. Theresulting suspension is stirred for 15 minutes at -40° C. and for 3hours at room temperature. An aqueous ammonium chloride solution is thenadded and the tetrahydrofuran is evaporated. The resulting aqueous phaseis extracted with chloroform. The chloroform phase is washed with water,dried with anhydrous sodium sulfate and evaporated to dryness, a crudeproduct being obtained which is purified by chromatography on silicagel, giving 1.02 g (2.6 mmol) of 4,5-dichloro-1-{4-4-hydroxy-4-(4-methylphenyl)-1-piperidyl!butyl}-2-methyl-1H-imidazole.

The spectroscopic data for the identification of this product are foundin Table I.

PROCESS G EXAMPLE 16a

Preparation of 1-4-(4-phenyl-1,2,3,6-tetrahydro-1-pyridyl)butyl!-1H-pyrazole.

2.0 g of LiAlH₄ are added to a solution of 3.3 g (10 mmol) of 1-4-(4-phenyl-1,2,3,6-tetrahydro-1-pyridyl)-3-oxobutyl!-1H-pyrazole in 25ml of THF. The resulting mixture is refluxed for 2 hours. The excessLiAlH₄ is destroyed by addition of concentrated NaOH and water. Theinorganic salts are filtered off and the THF is evaporated under vacuum,giving 2.6 g (8.2 mmol) of 1-4-(4-phenyl-1,2,3,6-tetrahydro-1-pyridyl)butyl!-1H-pyrazole.

The melting point and the spectroscopic data for the identification ofthis product are found in Table II.

PROCESS H EXAMPLE 11a

Preparation of the hydrochloride of 4,5-dichloro-2-methyl-1-4-(4-phenyl-1,2,3,6-tetrahydro-1-pyridyl)butyl!-1H-imidazole.

2.5 ml of an 8.4N hydrochloric acid/ethanol solution are added to asolution, cooled in an ice bath, of 7.4 g (20.3 mmol) of4,5-dichloro-2-methyl-1-4-(4-phenyl-1,2,3,6-tetrahydro-1-pyridyl)butyl!-1H-imidazole in 15 ml ofabsolute ethanol. After a few minutes, a precipitate appears which isfiltered, washed with cold ethanol and dried, 7.7 g (19.2 mmol) of4,5-dichloro-2-methyl-1-4-(4-phenyl-1,2,3,6-tetrahydro-1-pyridyl)-butyl!-1H-imidazolehydrochloride being obtained.

The melting point and the spectroscopic data for the identification ofthis product are found in Table II.

    TABLE I                                                                          -                                                                              ##STR14##                                                                      Ex R.sub.1 R.sub.2 R.sub.3 R.sub.4 R.sub.5 Z.sub.1 Z.sub.2 R.sub.6            Z.sub.4 n M.p. IR cm.sup.-1 .sup.1                                              H NMR (300 MHz), δ(solvent)                                               1 H H H H H N CH Cl CH 4 102-103° C. 3364(b.a. OH), 1.56(quin,        J=7.1Hz, 2H); 1.65(b.a. 1H); 1.76(d, J=12.4Hz, 2H); 1.90(quin,                              2950, 2810, 1375, J=7.6Hz, 2H); 2.20(m, 2H); 2.40-2.55(a.c.,       4H); 2.83(d, J=9.5Hz, 2H);                                                                 1130, 991, 969, 4.11(t, J=7Hz, 2H); 7.21-7.42(a.c., 5H);          7.52(d, J=8.5Hz, 2H)                                                                        760, 696, 605 (CDCl.sub.3)                                                     KBr                                                                 2 H H H H H CCH.sub.3 N Cl CCl 4 86-89° C. 3196(b.a., OH),            1.59(m, J=5.3 J'=6.6, 2H); 1.70-1.32(a.c., 4H); 2.16(d, t, J=13.0Hz                              2951, 2924, 2824, J'=4.4Hz, 2H); 2.37(s, 3H); 2.41-2.55      (a.c., 5H); 2.79(d, J=11.3Hz,                                                               1406, 1247, 1146, 2H); 3.88(t, J=7.5Hz, 2H); 7.27(t,              J=7.2Hz, 1H); 7.36(t, J=7.6Hz, 2H);                                                         762, 703 7.51(d, J=7.3Hz, 2H)(CDCl.sub.3)                                      KBr                                                                 3 H H H H H CH N CHCHCHCHC 4 122-123° C. 3180(b.a., OH),              1.51(quin, J=7.4Hz, 2H); 1.73(d, J=12.7Hz, 2H); 1.87(quin, J=7.6Hz,                             2929, 2818, 1496, 2H); 2.10(dt, J=12.9Hz J'=4.1Hz, 2H);       2.36-2.50(a.c., 4H); 2.70(d,                                                               1467, 1459, 1445, J=11.2Hz, 2H); 3.25(b.a., 1H); 4.12(t,           J=7.1Hz, 2H); 7.21-7.40(a.c.,                                                              1286, 1219, 1143, 6H); 7.51(d, J=8.3Hz, 2H); 7.70-7.75(a.c.,       2H)                                                                                        769, 743, 707 (CDCl.sub.3)                                                     KBr                                                                  4 H H H H H CH N H N 4 123° C. 3180(b.a., OH), 1.45(quin,             J=7.5Hz, 2H); 1.69(d, J=12.9Hz, 2H); 1.85(quin,                                             2949, 2919, 2838, J=7.5Hz, 2H); 2.07(dt, J=13.0Hz J'=4.1Hz,       2H); 2.33-2.45(a.c., 4H);                                                                   1276, 1145, 1135, 2.69(d, J=11.2Hz, 2H); 2.93(b.a., 1H);          4.10(t, J=6.9Hz, 2H); 7.18(t,                                                               1006, 770, 707, J=7Hz, 1H); 7.27(t, J=7.8Hz, 2H); 7.46(d,         J=8.3Hz, 2H); 7.80(s,                                                                       676 1H); 7.91(s, 1H)(CDCl.sub.3)                                               KBr                                                                 5 H H Cl H H N CH Cl CH 4 106° C. 3145(b.a., OH), 1.47(quin,          J=7.5Hz, 2H); 1.69(d, J=11.9Hz, 2H); 1.84(quin,                                             2947, 2918, 2834, J=7.6Hz, 2H); 2.05(dt, J=13Hz, J'=4.4Hz,        2H); 2.34-2.50(a.c., 5H);                                                                   1318, 1147, 1083, 2.72(d, J=11.2Hz, 2H); 4.05(t, J=7.0Hz,         2H); 7.29(syst. AB, J=8.6Hz,                                                                1112, 990, 817, 2H); 7.36(s, 2H); 7.42 (|syst AB,        J=8.6Hz, 2H)(CDCl.sub.3)                                                                    612                                                                            KBr                                                                 6 H H Cl H H CCH.sub.3 N Cl CCl 4 oil 3340(b.a., OH), 1.54(m, 2H);           1.67-1.78(a.c., 4H): 2.06(dt, J=13Hz, J'=4.2Hz, 2H);                                        2946, 2820, 1537, 2.32(s, 3H); 2.38-2.45(a.c., 5H); 2.73(d,       J=11.2Hz, 2H); 3.86(t, J=7.3Hz,                                                             1492, 1471, 1406, 2H); 7.28(syst AB, J=8.6Hz, 2H); 7.43(syst       AB, J=8.6Hz, 2H)(CDCl.sub.3)                                                               1376, 1247, 1135,                                                              1094, 1013, 828,                                                               755                                                                            film                                                                7 H CF.sub.3 H H H N CH Cl CH 4 oil 3360(b.a., OH), 1.48(quin,               J=7.6Hz, 2H; 1.71(d, J=12.5Hz, 2H); 1.85(quin, J=7.6Hz, 2H);                                2948, 2823, 1438, 2.06-2.21(a.c., 3H); 2.36-2.43(a.c., 4H);       2.76(d, J=11.5Hz, 2H); 4.06                                                                 1378, 1330, 1212, (t, J=7.1Hz, 2H); 7.35(s, 2H); 7.43-7.51(a      .c., 2H); 7.66(d, J=7.5Hz, 1H);                                                             1165, 1124, 1047, 7.79(2, 1H)(CDCl.sub.3)                                      972, 804, 704                                                                  film                                                                8 H CF.sub.3 H H H CCH.sub.3 N Cl CCl 4 oil 3340(b.a., OH), 1.57(quin,       J=7.5Hz, 2H); 1.70-1.80(a.c., 4H); 2.15(dt, J=12.9Hz                                        2948, 2823, 1408, J'=3.6Hz, 2H); 2.35(s, 3H); 2.40-2.52(a.c.      , 4H); 2.80(d, J=11.7Hz, 2H);                                                               1330, 1165, 1126, 3.88(t, J=7.0Hz, 2H); 7.42-7.57(a.c.,           2H); 7.69(d, J=7.5Hz, 1H);                                                                  1075, 789, 763, 7.82(s, 1H)(CDCl.sub.3)                                        704                                                                            film                                                                9 H H F H H CCH.sub.3 N Cl CCl 4 oil 3330(b.a., OH), 1.58(m, 2H);            1.64-1.81(a.c., 4H); 2.14(dt, J=12.9Hz J'=3.6Hz 2H); 2.32(s,                                2946, 2818, 1509, 3H); 2.43-2.60(a.c., 4H); 2.84(d, J=11Hz,       2H); 3.87(t, J=7.1Hz, 2H); 4.18                                                             1406, 1247, 1222, (b.a., 1H); 7.01(t, J=8.8Hz, 2H);               7.46(dd, J=8.8Hz J'=5.2Hz, 2H)(CDCl.sub.3)                                                  1160, 835                                                                      film                                                               10 H H H H H CH CH CHCHCHCHC 4 109-111° C. 3190(b.a., OH),             1.57(m, 2H); 1.73(d, J=14Hz, 2H); 1.80(b.a., 1H); 1.90(m, 2H); 2.13(dt,                     2956, 2823, 1461, J=13Hz J'=4Hz, 2H); 2.32-2.46(a.c., 4H);        2.76(d, J=11.3Hz, 2H); 4.16(t,                                                             1446, 1319, 1303, J=7.1Hz, 2H); 6.50(d, J=3.1Hz, 1H);              7.05-7.14(a.c., 2H); 7.18-7.40(a.c.,                                                       1218, 1142, 738, 5H); 7.50(d, J=7.8Hz, 2H); 7.00(d, J=7.3Hz,       1H)(CDCl.sub.3)                                                                            703                                                                            KBr                                                                 11 H H CH.sub.3 H H CCH.sub.3 N Cl CCl 4 oil 3360(b.a., OH) 1.53(m,           2H); 1.66-1.84(a.c., 4H); 2.09(dt, J=12.9Hz, J'=3.6Hz, 2H);                                 2946, 2818, 1535, 2.33(s, 3H); 2.36(s, 3H); 2.39-2.50(a.c.,       4H); 2.77(d, J=11.2Hz, 2H);                                                                 1471, 1406, 1376, 3.87(t, J=7.0Hz, 2H); 7.15(syst AB,             J=7.8Hz, 2H);                                                                               1247, 1134, 817, 7.33(syst AB, J=7.8Hz, 2H)(CDCl.sub.3)                            755                                                                        film                                                               12 H H H H H N CH H CH 4 89-91° C. 3137(b.a., OH) 1.51(quin,           J=7.6Hz, 2H); 1.73(d, J=12.3Hz, 2H); 1.89(quin, J=7.6Hz,                                    2947, 2532, 1396, 2H); 2.00-2.20(a.c., 3H); 2.35-2.45(a.c.,       4H); 2.76(d, J=10.2Hz, 2H);                                                                 1378, 1119, 1046, 4.13(t, J=7.1Hz, 2H); 6.21(s, 1H);              7.21(m, 1H); 7.30-7.37                                                                      756, 697 (a.c., 3H); 7.44-7.52(a.c., 3H)(CDCl.sub.3)                                  KBr                                                         13 H H H H H N CH CHCHCHCHC 4 107-109° C. 3311(b.a., OH) 1.53(m,       2H); 1.71(d, J=12.2Hz, 2H); 1.95(m, 2H) 2.10(m, 2H); 2.29(b.a.,                            2953, 2803, 1465, 1H); 2.35-2.47(a.c., 4H); 2.71(d, 2H);           4.39(t, J=7.1Hz, 2H); 7.13(t, 1H);                                                         1375, 1133, 1117, 7.22-7.44(a.c., 5H); 7.50(d, J=8Hz, 2H);         7.71(d, J=8.3Hz, 1H);                                                                      1043, 1017, 761, 7.95(s, 1H)(CDCl.sub.3)                                       744, 704                                                                       KBr                                                                 14 H H H H H N CCHCHCHCH CH 4 120-122° C. 3295(b.a., OH) 1.58(m,       2H); 1.73(d, J=13.5Hz, 2H); 1.90-2.20(a.c., 5H); 2.38-2.47(a.c.,                                   2946, 2817, 1377, 4H); 2.75(d, J=10.5Hz, 2H);              4.42(t, J=6.6Hz, 2H); 7.06(t, J=7.5Hz, 1H);                                                1126, 786, 735, 7.22-7.37(a.c., 4H); 7.49(d, J=7.8Hz, 2H);         7.61-7.71(a.c., 2H);                                                                       700 7.90(s, 1H)(CDCl.sub.3)                                                    KBr                                                                 15 H H CH.sub.3 H H N CH Cl CH 4 81-82° C. 3122(b.a., OH)              1.51(quin, J=7.6Hz, 2H); 1.73(d, J=11.7Hz, 2H); 1.87(quin, J=7.6Hz,                              2936, 1475, 1434, 2H); 2.12(dt, J=12.8Hz J'=4.4Hz,           2H); 2.33(s, 3H); 2.35-2.48(a.c.,                                                           1378, 1319, 989, 5H); 2.74(d, J=11.2Hz, 2H); 4.07(t,              J=7.1Hz, 2H); 7.15(d, J=8Hz, 2H);                                                           973, 814 7.25-7.40(a.c., 4H)(CDCl.sub.3)                                       KBr                                                                16 H H CH.sub.3 O H H N CH Cl CH 4 122-123° C. 3190(b.a., OH)          1.49(quin, J=7.6Hz, 2H); 1.72(d, J=11.8Hz, 2H); 1.84(quin, J=7.4Hz,                              2954, 2923, 2827, 2H); 2.00-2.14(a.c.(dt+b.a.), 3H);         2.34-2.47(a.c., 4H); 2.72(d, J=11Hz,                                                        1509, 1314, 1243, 2H); 3.77(s, 3H); 4.05(t, J=7.1Hz, 2H);         6.85(d, J=9Hz, 2H); 7.24-7.42                                                               1178, 971 (a.c., 4H)(CDCl.sub.3)                                   17 H H H H H CPh N H CH 4 108-110° C. 3220(b.a., OH) 1.45(quin,        J=7.6Hz, 2H); 1.68-1.82(a.c., 4H); 2.08(dt, J=13.0Hz                                        2944, 2817, 1473, J'=4.1Hz, 2H); 2.29-2.42(a.c., 4H);             2.51(b.a., 1H); 2.67(d, J=11.2Hz,                                                           1446, 1421, 1136, 2H); 4.01 m(t, J=7.3Hz, 2H); 7.01(s, 1H);       7.08(s, 1H); 7.20-7.56(a.c.,                                                                1046, 787, 773, 10H)(CDCl.sub.3)                                               761, 700                                                                       film                                                               18 H H CH.sub.3 H H CH N CHCHCHCHC 4 oil 3260(b.a., OH) 1.58(quin,            J=7.6Hz, 2H); 1.74(d, J=12Hz, 2H); 1.82(b.a., 1H); 1.95(quin,                              2944, 2817, 1497, J=7.6Hz, 2H); 2.11(dt, 2H); 2.33(s, 3H);         2.40-2.50(a.c., 4H); 2.74(d,                                                               1459, 1381, 1287, J=11.5Hz, 2H); 4.20(t, J=7.1Hz, 2H);             7.15(d, J=8.3Hz, 2H); 7.22-7.35                                                            1135, 1046, 817, (a.c., 3H); 7.37-7.43(a.c., 2H); 7.79(m,          1H); 7.87(s, 1H)(CDCl.sub.3)                                                               745                                                                            film                                                                19 H H H H H CH N Ph CPh 4 138-139° C. 3194(b.a., OH) 1.38(m,          2H); 1.56(m, 2H); 1.72(d, J=12.4Hz, 2H); 2.09(dt, 2H); 2.25(t,                              2939, 3806, 1509, J=7.4Hz, 2H); 2.39(m, 2H); 2.66(m, 2H);         3.10(b.a., 1H); 3.78(t, J=7.2Hz,                                                            1446, 773, 766, 2H); 7.10-7.52(a.c., 16H);                                     758, 696                                                                       KBr                                                                20 CHCHCHCH H H H N CH Cl CH 4 oil 3357(b.a., OH), 1.44(quin, J=7.3Hz,        2H); 1.77(quin, J=7.5Hz, 2H); 2.15-2.30(a.c., 5H);                                         2946, 2833, 1434, 2.34(t, J=7.5Hz, 2H); 2.57(m, 2H); 2.73(d,       J=11.3Hz, 2H); 3.99(t,                                                                     1379, 1315, 1140, 2H); J=7.1Hz, 7.26-7.46(a.c., 6H); 7.73(d,       J=8.1Hz, 1H); 7.82(m,                                                                      1123, 972, 781, 1H); 8.91(m, 1H)(CDCl.sub.3)                                   613                                                                            KBr                                                                 21 H CHCHCHCH H H N CH Cl CH 4 142-143° C. 3131(b.a., OH),             1.55(quin, J=7.5Hz, 2H); 1.70-1.97(a.c., 5H); 2.29(dt, J=12.7Hz,                                   2950, 2820, 1377, J'=4.1Hz, 2H); 2.41-2.55(a.c.,           4H); 2.83(d, J=11.7Hz, 2H);                                                                1311, 971, 829, 4.11(t, J=7.0Hz, 2H); 7.39-7.50(a.c., 4H);         7.64(dd, J=9.1Hz,                                                                          761, 613 J'=1.5Hz, 1H); 7.81-7.85(a.c., 3H); 7.95(s, 1H)                           KBr CDCl.sub.3)                                                 Ex R.sub.1 R.sub.2 R.sub.3 R.sub.4 R.sub.5 Z.sub.1 Z.sub.2 R.sub.6            Z.sub.4 n Salt/M.p. IR cm.sup.-1 .sup.1 H NMR(300 MHz), δ,               J=Hz(solvent)                                                                   22 H H H H H N CH                                                              ##STR15##                                                                      CH 4 137-140° C. 3347, 2944, 2810,1562, 1492, 1376,1127, 1094,         1002,952, 828, 760,699KBr 1.56(m, 2H); 1.74(m, 2H); 1.80(b.a., 1H);            1.94(m, 2H); 2.40(dt,J=13.1Hz, J'=4.0Hz, 2H); 2.40-2.50(a.c., 4H);             2.77(m, 2H); 4.15(t,J=7.0Hz, 2H); 7.25-7.40(a.c., 7H); 7.50(d, J=8.3Hz,        2H);7.61(s, 1H); 7.72(s, 1H)(CDCl.sub.3)                                                                                                                2     3 H H F H H CH N CHCHCHCHC 4 120-122° C. 3230, 2947, 2915,              1.58(m, 2H); 1.70(m, 2H); 1.93(m, 2H); 2.12(m, 2H);                                        1504, 1219, 1135, 2.40-2.55(a.c., 4H); 2.76(m, 2H); 4.19(t,        J=7.0Hz, 2H); 7.02(m, 2H);                                                                 835, 746 7.26(m, 2H); 7.30-7.50(a.c., 3H); 7.74(m, 1H);            7.83(s, 1H)(CDCl.sub.3)                                                                    KBr                                                                 24 H CCF.sub.3 H H H N CH Cl CH 4 HCl 3259, 2465, 2420, 1.62-1.84(a.c.,       6H); 2.53(m, 2H); 3.09-3.40(a.c., 6H);                                                     147-148° C. 2365, 1328, 1108, 4.12(t, J=6.8Hz, 2H);         5.76(s, 1H); 7.51(s, 1H); 7.52-7.82(a.c., 4H);                                              1073 8.02(s, 1H); 10.96(b.a., 1H)(DMSO-d.sub.6)                                KBr                                                                25 H H F H H N CH CHCHCHCHC 4 136-137° C. 3303, 2951, 2805,            1.54(m, 2H); 1.60-1.80(a.c., 3H); 1.97(m, 2H); 2.06(dt, J=13.0Hz,                                 1506, 1464, 1376, J'=4.3Hz, 2H); 2.30-2.43(a.c. 4H;         2.72(m, 2H); 4.40(t, J=7.0Hz,                                                              1218, 1162, 1118, 2H); 6.99(t, J=8.8Hz, 2H); 7.12(m, 1H);          7.32-7.47(a.c., 4H);                                                                       832, 741 7.71(d, J=8.1Hz, 1H); 7.96(s, 1H)(CDCl.sub.3CD.sub.3       OD 1:1!)                                                                                  KBr                                                                 26 H H F H H N CCHCHCHCH CH 4 148-150° C. 3325, 2950, 2923,            1.57(m, 2H); 1.70-1.77(a.c., 3H); 1.98-2.19(a.c., 4H); 2.35-2.49(a.c.,                       2812, 1509, 1377, 4H); 2.77(d, J=11.2Hz, 2H); 4.45(t,            J=7.0Hz, 2H); 6.98-7.15(a.c., 3H);                                                         1218, 1131, 834, 7.25-7.49(a.c., 3H); 7.63(d, J=8.3Hz, 1H);        7.69(d, J=7.8Hz, 1H); 7.91                                                                 758 (s, 1H)(CDCl.sub.3CD.sub.3                                      OD :1!)                                   KBr                                  27 H H F H H N CCHCHCHCH N 4 109-110° C. 3400, 2931, 2812,             1.47-1.80(a.c., 4H); 1.90-2.25(a.c., 5H); 2.30-2.55(a.c., 4H); 2.70(m,                       1509, 1229, 1101, 2H); 4.78(t, J=6.9Hz, 2H); 7.01(t,             J=8.7Hz, 2H); 7.26-7.54(a.c., 4H);                                                         831, 745 7.85(dd, J=6.7Hz, J'=3.0Hz, 2H)(CDCl.sub.3CD.sub.3        OD 1:1!)                                                                                   KBr                                                                 28 H H F H H N N CHCHCHCHC 4 102-103° C. 3430, 2952, 2925,             1.45-1.80(a.c., 4H); 1.85-2.25(a.c., 5H); 2.25-2.55(a.c., 4H); 2.77                             1508, 1223, 1140, (m, 2H); 4.69(t, J=6.9Hz, 2H);              7.01(t, J=8.7Hz, 2H); 7.26-7.53(a.c.,                                                      833, 744 5H); 8.06(d, J=7.3Hz, 1H)(CDCl.sub.3CD.sub.3              OD 1:1!)                                                                                   KBr                                                           

    TABLE II                                                                         -                                                                              ##STR16##                                                                                                                                              E     x R.sub.1 R.sub.2 R.sub.3 R.sub.4 R.sub.5 Z.sub.1 Z.sub.2 R.sub.6              Z.sub.4 n M.p. IR cm.sup.-1 .sup.1                                              H NMR(300 MHz), δ(solvent)                                                1a H H H H H N CH Cl CH 4 62-64°                                       C. 3113, 2920, 2745, 1.56(quin, J=7.6Hz, 2H); 1.91(quin J=7.6Hz, 2H);         2.47                                                                                        1375, 1325, 1138, (t, J=7.4Hz, 2H); 2.58(m, 2H); 2.65(t,          J=5.6Hz, 2H); 3.14                                                                          965, 837, 742, 688 (m, 2H); 4.11(t, J=7.1Hz, 2H); 6.06(m,         1H); 7.23-7.42                                                                              KBr (a.c., 7H)(CDCl.sub.3)                                          2a H H H H H CH N CHCHCHCHC 4 66-69° C. 2933, 1495, 745,              1.55(quin, J=7.6Hz, 2H); 1.92(quin, J=7.6Hz, 2H); 2.43                                     694, 665 (t, J=7.3Hz, 2H); 2.52(m, 2H); 2.61(t, J=5.6Hz,           2H); 3.07                                                                                  film (m, 2H); 4.14(t, J=7.1Hz, 2H); 6.02(m, 1H); 7.20-7.40                        (a.c., 8H); 7.80(m, 1H); 7.86(s, 1H)(CDCl.sub.3)                  3a H H H H H CH N H N 4 63-64° C. 2942, 1438, 1381, 1.56(m,           2H); 1.95(m, 2H); 2.47(t, J=7.1Hz, 2H); 2.56                                                1271, 1142, 1006, (m, 2H); 2.66(t, J=5.3Hz, 2H); 3.11(m,          2H); 4.19                                                                                   753, 697, 681, (t, J=7.0Hz, 2H); 6.05(s, 1H); 7.21(m, 1H);        7.30                                                                                        KBr (t, J=7.6Hz, 2H); 7.36(d, J=7.8Hz, 2H); 7.94(s, 1H);          8.06                                                                                         (s, 1H)(CDCl.sub.3)                                                4a H H Cl H H N CH Cl CH 4 103-104° C. 2939, 1493, 1436,              1.54(m, 2H); 1.90(m, 2H); 2.45(t, J=7.4Hz, 2H); 2.51                                        1381, 1306, 1122, (m, 2H); 2.65(t, J=5.6Hz, 2H); 3.10(m,          2H); 4.10                                                                                   1097, 973, 843, 824, (t, J=7.0Hz, 2H); 6.03(m, 1H);               7.26(syst AB, J=8.6Hz,                                                                      730 2H); 7.29(syst AB, J=8.6Hz, 2H); 7.37(s, 1H); 7.41                              KBr (s, 1H)(CDCl.sub.3)                                        5a H H Cl H H CCH.sub.3 N Cl CCl 4 119-120° C. 2922, 1531,            1494, 1.59(m, 2H); 1.76(m, 2H); 2.36(s, 3H); 2.42-2.53(a.c.,                                1469, 1403, 1380, 4H); 2.67(t, J=5.3Hz, 2H); 3.12(m, 2H);         3.88(t, J=7.4Hz,                                                                            1366, 1245, 10-94, 2H); 6.04(m, 1H); 7.27(syst AB, J=9.1Hz,       2H); 7.30                                                                                   KBr (syst AB, J=9.1Hz, 2H)(CDCl.sub.3)                              6a H CF.sub.3 H H H N CH Cl CH 4 oil 2944, 1434, 1375, 1.53(quin,            J=7.5Hz, 2H); 1.89(quin, J=7.7Hz, 2H); 2.45                                                 1331, 1247, 1165, (t, J=7.3Hz, 2H); 2.54(m, 2H); 2.66(t,          J=5.5Hz, 2H); 3.10                                                                          1126, 1076, 972, 800 (m, 2H); 4.08(t, J=7.1Hz, 2H); 6.10(m,       1H); 7.35-7.56                                                                              698 (a.c., 5H); 7.59(s, 1H)(CDCl.sub.3)                                        film                                                                7a H CF.sub.3 H H H CCH.sub.3 N Cl CCl 4 oil 2931, 2815, 1533,               1.62(quin, J=6.6Hz, 2H); 1.77(quin, J=7.6Hz, 2H); 2.37                                      1405, 1331, 1246, (s, 3H); 2.51(t, J=7.2Hz, 2H); 2.60(m,          2H); 2.71                                                                                   1165, 1125, 1076, (t, J=5.6Hz, 2H); 3.17(m, 2H); 3.89(t,          J=7.3Hz, 2H); 6.14                                                                          797, 699 (m, 1H); 7.40-7.50(a.c., 2H); 7.55(d, J=7.5Hz,           1H); 7.62                                                                                   film (s, 1H)(CDCl.sub.3)                                            8a H H F H H N CH Cl CH 4 86-87°                                       C. 2936, 1512, 1378, 1.60(quin, J=7.5Hz, 2H); 1.91(quin, J=7.5Hz, 2H);                      1326, 1229, 988, 967 2.50-2.82(a.c., 4H); 2.76(t, J=5.6Hz,       2H); 3.19(m, 2H);                                                                           KBr 4.11(t, J=6.9Hz, 2H); 5.97(s, 1H); 6.99(t, J=8.8Hz,           2H);                                                                                         7.32(dd, J=8.8Hz J'=5.4Hz, 2H); 7.38(s, 1H); 7.40(s, 1H)                         (CDCl.sub.3)                                                     9a H H F H H CCH.sub.3 N Cl CCl 4 79-82° C. 2934, 1531, 1512,         1.59(m, 2H); 1.76(m, 2H); 2.37(s, 3H);                                                      1408, 1247, 1225, 2.48(t, J=7.2Hz, 2H); 2.54(m, 2H); 2.67;        99                                                                                          1167, 818 (t, J=5.6Hz, 2H); 3.12(m, 2H); 3.89(t, J=7.3Hz,                        KBr 2H); 5.99(m, 1H); 6.99(t, J=8.7Hz, 2H); 7.33                              (dd, J=8.7Hz J'=5.4Hz, 2H)(CDCl.sub.3)                            10a H H H H H CCH.sub.3 N Cl CCl 4 oil 2929, 1533, 1405, 1.59(m, 2H);         1.76(m, 2H); 2.37(s, 3H); 2.49(t, J=7.3Hz,                                                  1246, 748 2H); 2.58(m, 2H); 2.69(t, J=5.4Hz, 2H); 3.14(m,         2H);                                                                                        film 3.89(t, J=7.4Hz, 2H); 6.06(m, 1H); 7.22-7.40(a.c., 5H)                     (CDCl.sub.3)                                                      11a H H H H H CCH.sub.3 N Cl CCl 4 HCl 2930, 2576, 1407, 1.69(m, 2H);         1.81(m, 2H); 2.35(s, 3H); 2.71(d, J=7.2Hz,                                                 203-204°C. 1376, 1245, 750, 1H); 2.91(m, 1H);               3.17(a.c., 3H); 3.56(m, 1H); 3.75                                                           KBr (m, 1H); 3.90-3.97(a.c., 3H); 6.17(s, 1H); 7.25-7.40                           (a.c., 3H); 7.47(d, J=7.6Hz, 2H); 11.30(b.a., 1H)                                 (DMSO-d.sub.6)                                              12a H H H H H CCH.sub.3 N Cl CCl 4 HCl 3569, 2941, 2692, 1.67(m, 2H);         1.79(m, 2H); 2.36(s, 3H); 2.69(d, J=18.0Hz,                                                192-194° C. 2556, 1601, 1446, 1H); 2.88(m, 1H);             3.15(a.c., 3H); 3.54(m, 1H); 3.72                                                           769, 753, 698 (m, 1H); 3.85-3.98(a.c., 3H); 6.15(s, 1H);          7.22-7.38(a.c.,                                                                             KBr 3H); 7.45(d, J=7.3Hz, 2H); 9.93(b.a., 1H); 11.36(b.a.,        1H)                                                                                          (DMSO-d.sub.6)                                                    13a H H F H H CH CH CHCHCHCHC 4 oil 2937, 1510, 1464, 1.61(quin,              J=7.7Hz, 2H); 1.93(quin, J=7.6Hz, 2H);                                                     1230, 1161, 816, 742 2.42-2.58(a.c., 4H); 2.66(t, J=5.6Hz,         2H); 3.11(m, 2H);                                                                          film 4.17(t, J=7.0Hz, 2H); 5.98(m, 1H); 6.51(d, J=3.9Hz,           1H);                                                                                        6.95-7.39(a.c., 8H); 7.65(d, J=7.8Hz, 1H)(CDCl.sub.3)                    14a H H H H H CH CH CHCHCHCHC 4 oil 2938, 1510, 1485, 1.63(quin,        J=7.4Hz, 2H); 1.94(quin, J=7.4Hz, 2H); 2.49                                                1463, 1446, 1376, (t, J=7.6Hz, 2H); 2.60(m, 2H); 2.69(t,           J=5.3Hz, 2H); 3.14                                                                         1336, 1315, 763, (m, 2H); 4.19(t, J=7.1Hz, 2H); 6.08(m, 1H);       6.53(m, 1H);                                                                               740, 695 7.08-7.44(a.c., 9H); 7.67(d, J=8.1Hz, 1H)(CDCl.sub.3      )                                                                                           film                                                               15a H H CH.sub.3 H H CCH.sub.3 N Cl CCl 4 87-88° C. 2939, 2916,        1529, 1.59(m, 2H); 1.75(m, 2H); 2.32(s, 3H); 2.36(s, 3H);                                   1404, 1378, 1243, 2.47(t, J=7.2Hz, 2H); 2.54(m, 2H);              2.67(t, J=5.2Hz, 2H);                                                                       1166, 1131, 1016 3.11(m, 2H,); 3.87(t, J=7.3Hz, 2H);              6.01(s, 1H); 7.11                                                                           film (syst AB, J=8.1Hz, 2H); 7.27(syst AB, J=8.1Hz,                                     2H)(CDCl.sub.3)                                           16a H H H H H N CH H CH 4 36-38° C. 2941, 1396, 748, 695               1.54(quin, J=7.6Hz, 2H); 1.91(quin, J=7.6Hz, 2H); 2.45                                      film (t, J=7.6Hz, 2H); 2.55(m, 2H); 2.65(t, J=5.6Hz, 2H);         3.11                                                                                         (m, 2H); 4.14(t, J=7.1Hz, 2H); 6.03(m, 1H); 6.21(m, 1H);                         7.20-7.39(a.c., 6H); 7.49(m, 1H)(CDCl.sub.3)                    17a H H H H H N CH CHCHCHCHC 4 50-52° C. 2942, 1465, 1158,             1.61(quin, 2H); 2.00(quin, J=7.5Hz, 2H); 2.43-2.58(a.c.,                                   832, 740, 691 4H); 2.68(m, 2H); 3.14(s, 2H); 4.43(t,               J=6.6Hz, 2H); 6.02                                                                         KBr (s, 1H): 7.13(t, J=7.3Hz, 1H); 7.20-7.51(a.c., 7H); 7.73                    (d, J=7.9Hz, 1H) 7.99(s, 1H)(CDCl.sub.3)                           18a H H H H H N CCHCHCHCH CH 4 73-75° C. 3049, 2940, 2778,             1.60(quin, J=7.6Hz, 2H); 2.09(quin, J=7.4Hz, 2H); 2.48                                     1467, 1371, 1158, (t, J=7.4Hz, 2H); 2.55(m, 2H); 2.66(t,           J=5.6Hz, 2H); 3.11                                                                         1143, 1131, 757, 742, (d, J=2.9Hz, 2H); 4.45(t, J=7.1Hz,           2H); 6.03(s, 1H); 7.07                                                                     692 (t, J=7.5Hz, 1H); 7.20-7.39(a.c., 6H); 7.63(d, J=4.3Hz,                     KBr 1H); 7.70(d, J=8Hz, 1H); 7.91(s, 1H)(CDCl.sub.3)                      19a H H CH.sub.3 H H N CH Cl CH 4 72-73° C. 3115, 2938,         2740, 1.55(quin, 2H); 1.90(quin, J=7.5Hz, 2H); 2.33(s, 3H);                                 1376, 1328, 1137, 2.46(t, J=7.5Hz, 2H); 2.55(m, 2H);              2.66(t, J=6.4Hz, 2H);                                                                       986, 966, 844, 824 3.11(m, 2H); 4.10(t, J=7.0Hz, 2H);             6.01(s, 1H); 7.12                                                                           797 (syst AB, J=8Hz, 2H); 7.27(syst AB, J=8Hz, 2H);                                    KBr 7.37(s, 1H); 7.41(s, 1H)(CDCl.sub.3)                   20a H H CH.sub.3 O H H N CH Cl CH 4 104-105° C. 2923, 1533,            1405, 1.54(quin, 2H); 1.89(quin, J=7.6Hz, 2H); 2.44(t, J=7.4Hz,                             1379, 1246, 749 2H); 2.52(m, 2H); 2.65(t, J=5.3Hz, 2H);           3.10(m, 2H);                                                                                KBr 3.78(s, 3H); 4.09(t, J=7.0Hz, 2H); 5.95(s, 1H); 6.84                           (syst AB, J=8.5Hz, 2H); 7.31(syst AB, J=8.5Hz, 2H);                             7.36(s, 1H); 7.40(s, 1H)(CDCl.sub.3)                          21a H H H H H N CH Cl CH 3 oil 2948, 2923, 2811, 2.08(quin, J=7.0Hz,          2H); 2.42(t, J=7.0Hz, 2H); 2.58                                                             2774, 1446, 1382, (m, 2H); 2.67(t, J=5.6Hz, 2H); 3.13(m,          2H); 4.17                                                                                   1316, 971, 748, (t, J=6.9Hz, 2H); 6.07(m, 1H); 7.23-7.45(a.c      ., 7H)(CDCl.sub.3)                                                                          695                                                                            film                                                               22a H H H H H CCH.sub.3 N Cl CCl 3 oil 2923, 1533, 1405, 1.95(quin,           J=7.2Hz, 2H); 2.39(s, 3H); 2.46(t, J=7.0Hz,                                                 1379, 1246, 749 2H); 2.58(m, 2H); 2.69(t, J=4.9Hz, 2H);           3.13(m, 2H);                                                                                film 3.96(t, J=7.3Hz, 2H); 6.07(m, 1H); 7.20-7.41(a.c., 5H)                     (CDCl.sub.3)                                                      23a H H H H H CPh N H CH 4 oil 2940, 1496, 1474, 1.51(m, 2H); 1.81(m,         2H); 2.40(t, J=7.4Hz, 2H); 2.56                                                             1445, 1379, 1275, (m, 2H); 2.63(t, J=4.9Hz, 2H); 3.09(m,          2H); 4.04(t, J=                                                                             774, 698 7.2Hz, 2H); 6.03(m, 1H); 7.03(m, 1H); 7.13(m, 1H);                    film 7.22-7.48(a.c., 8H); 7.58(m, 2H)(CDCl.sub.3)                  24a H H CH.sub.3 H H CH N CHCHCHCHC 4 90-91° C. 2939, 2915,            1500, 1.59(m, 2H); 1.95(m, 2H); 2.32(s, 3H); 2.46(t, J=7.3Hz,                              1461, 1377, 1365, 2H); 2.53(m, 2H); 2.63(t, J=5.5Hz, 2H);          3.08(m, 2H);                                                                               750 4.20(t, J=6.95Hz, 2H); 6.00(s, 1H); 7.11(d, J=7.8Hz,           2H);                                                                                       KBr 7.27(a.c., 4H); 7.40(m, 1H); 7.80(m, 1H); 7.89(s, 1H)                          (CDCl.sub.3)                                                    25a H H H H H CH N Ph CPh 4 100-101° C. 3130, 2939, 2770,              1.46(quin, J=7.5Hz, 2H); 1.65(quin, J=7.6Hz, 2H); 2.33                                      1600, 1506, 1443, (t, J=7.3Hz, 2H); 2.53(m, 2H); 2.60(m,          2H); 3.05(m, 2H);                                                                           1259, 954, 780, 774, 3.84(t, J=7.2Hz, 2H); 6.02(m, 1H);           7.05-7.50(a.c., 15H);                                                                       750, 696, 649 7.61(s, 1H)(CDCl.sub.3)                                          KBr                                                                26a CHCHCHCH H H H N CH Cl CH 4 oil 3057, 3043, 2942, 1.61(quin,              J=7.5Hz, 2H); 1.95(quin, J=7.6Hz, 2H);                                                     2806, 2768, 1378, 2.51-2.57(a.c., 4H); 2.76(t, J=5.6Hz, 2H);       3.20(m, 2H);                                                                               1365, 971, 801, 778 4.14(t, J=7.1Hz, 2H); 5.74(m, 1H);             7.26-7.50(a.c., 6H);                                                                       film 7.75(d, J=8Hz, 1H); 7.84(m, 1H); 8.02(m, 1H);                              (CDCl.sub.3)                                                       27a H CHCHCHCH H H N CH Cl CH 4 95-96° C. 3111, 2920, 2806,            1.57(m, 2H); 1.92(m, 2H); 2.48(m, 2H); 2.71                                                1374, 1326, 966, (a.c., 4H); 3.18(m, 2H); 4.11(m, 2H);             6.22(m, 1H);                                                                               826, 749, 612, 7.38-7.50(a.c., 4H); 7.61(m, 1H); 7.75-7.84(a.      c., 4H)                                                                                    KBr (CDCl.sub.3)                                                    Ex R.sub.1 R.sub.2 R.sub.3 R.sub.4 R.sub.5 Z.sub.1 Z.sub.2 R.sub.6            Z.sub.4 n Salt/M.p. IR cm.sup.-1 .sup.1 H NMR(300 MHz), δ,               J=Hz(solvent)                                                                   28a H H F H H CH N CHCHCHCHC 2 135-136° C. 3050, 2920, 2780,           2.54(m, 2H); 2.74(t, J=5.6Hz, 2H); 2.92(t, J=6.7Hz, 2H);                                   2760, 1510, 1492, 3.24(m, 2H); 4.35(t, J=6.7Hz, 2H); 5.98(m,       1H); 7.00                                                                                  1459, 1224, 1202, (t, J=8.7Hz, 2H); 7.26-7.40(a.c., 4H);           7.42(m, 1H); 7.81                                                                          1161, 771, 751 (m, 1H); 8.01(s, 1H)(CDCl.sub.3)                                KBr                                                                 29a H H H H H CH N CHCHCHCHC 4 HCl 2940, 2488, 1500, 1.70-1.90(a.c.,          4H); 2.78(m, 2H); 3.17(m, 2H);                                                            177-178° C. 1420, 1390, 742 3.20-3.50(b.a., 2H);             3.79(m, 2H); 4.30(td, J=6.6Hz, 2H);                                                        KBr 6.15(s, 1H); 7.17-7.40(a.c., 5H); 7.45(d, J=7.3Hz, 2H);                      7.65(m, 2H); 8.35(s, 1H)(DMSO-d.sub.6)                            30a H H F H H CH N CHCHCHCHC 4 106-108° C. 2942, 1512, 1498,           1.59(quin, J=7.5Hz, 2H); 1.96(quin, J=7.5Hz, 2H); 2.40-                                    1460, 1376, 1221, 756 2.50(a.c., 4H); 2.63(t, J=5.5Hz, 2H);        3.09(m, 2H); 4.21                                                                          KBr (t, J=7.1Hz, 2H); 5.97(m, 1H); 6.98(t, J=8.1Hz, 2H);                            7.20-735(a.c., 4H); 7.40(m, 1H); 7.80(m, 1H); 7.89(s,                        1H)(CDCl.sub.3)                                                  31a H H F H H CH N CHCHCHCHC 4 HCl 2930, 1600, 1510, 1.70-2.00(a.c.,          4H); 2.78(m, 2H); 3.20(m, 2H); 3.20-                                                       1275 3.60(b.a., 2H); 3.81(m, 2H); 4.38(t, J=6.6Hz, 2H); 6.13                   KBr (s, 1H); 7.19(t, J=8.7Hz, 2H); 7.33(m, 2H); 7.49(m,                              2H); 7.71(d, J=7.8Hz, 1H); 7.77(d, J=7.6Hz, 1H);             8.79(s,                                                                                     1H); 11.20(b.a., 1H)(DMSO-d.sub.6)                                 32a H CF.sub.3 H H H CCH.sub.3 N Cl CCl 4 HCl 2930, 2490, 1330, 1.67(m,       2H); 1.79(m, 2H); 2.33(s, 3H); 2.79(m, 1H);                                                205-206°                                                     C. 1243, 1164, 119, 2.91(m, 1H); 3.10-3.20(a.c., 3H); 3.55(m, 1H); 3.77                    1076 (m, 1H); 3.91-4.00(a.c., 3H); 6.33(s, 1H); 7.58-7.80                        KBr (a.c., 4H); 11.32(b.a., 1H)(DMSO-d.sub.6)                    33a H H F H H N CH Cl CH 4 HCl 2543, 1512, 1232, 1.71-1.85(a.c., 4H);         2.68(m, 1H); 2.86(m, 1H); 3.10-                                                            191-192° C. 967, 807 3.20(a.c., 3H); 3.55(m, 1H);           3.72(m, 1H); 3.90(m,                                                                        KBr 1H); 4.12(t, J=6.5Hz, 2H); 6.14(s, 1H); 7.20(t,               J=8.7Hz,                                                                                     2H); 7.40-7.55(a.c., 3H); 8.06(s, 1H); 11.20(b.a., 1H)                             (DMSO-d.sub.6)                                                34a H H H H H N CH CHCHCHCHC 4 HCl 2931, 2566, 742 1.80(m, 2H); 1.91(m,       2H); 2.67(m, 1H); 2.88(m, 1H);                                                            193-194° C. KBr 3.10-3.20(a.c., 3H); 3.52(m, 1H);            3.71(m, 1H); 3.90                                                                           (m, 1H); 4.46(t, J=6.7Hz, 2H); 6.15(s, 1H); 7.14                               (t, J=7.5Hz, 1H); 7.25-7.41(a.c., 4H); 7.46(d, J=8.6Hz,                            2H); 7.71(d, J=8.6Hz, 1H); 7.75(d, J=8.3Hz, 1H);              8.08(s,                                                                                     1H); 11.18(b.a., 1H)(DMSO-d.sub.6)                                 35a H H F H H CCH.sub.3 N Cl CCl 4 HCl 2930, 2590, 1512, 1.67(m, 2H);         1.79(m, 2H); 2.33(s, 3H); 2.67(m, 1H);                                                     160-161°                                                     C. 1409, 1241, 827 2.90(m, 1H); 3.10-3.25(a.c., 3H); 3.54(m, 1H); 3.72                      KBr (m, 1H); 3.85-3.98(a.c., 3H); 6.13(s, 1H); 7.19(m,           2H);                                                                                         7.50(m, 2H); 11.28(b.a., 1H)(DMSO-d.sub.6)                       36a H H H H H N CH                                                              ##STR17##                                                                      CH 4 HCl198-199° C. 2472, 1560, 1450,1095, 955, 810, 745KBr            1.77(m, 2H); 1.87(m, 2H); 2.70(m, 1H); 2.86(m, 1H);3.16(a.c., 3H);             3.55(m, 1H); 3.73(m, 1H); 3.90(m,1H); 4.17(t, J=6.6Hz, 2H); 6.15(m, 1H);       7.25-7.47(a.c.,7H); 7.59(m, 2H); 7.90(s, 1H); 8.27(s, 1H); 10.91(b.a.,1H)      (DMSO-d.sub.6)                                                                 37a H H H H H N CH                                                              ##STR18##                                                                      CH 4 126-127° C. 2935, 1570, 1493,1455, 1379, 1091,953, 815,           746KBr 1.60(m, 2H); 1.97(m, 2H); 2.48(t, J=7.3Hz, 2H); 2.56(m, 2H);            2.67(t, J=5.1Hz, 2H); 3.13(m, 2H); 4.18(t, J=7.1Hz, 2H); 6.05(m, 1H);          7.23-7.40(a.c., 9H); 7.61(s, 1H); 7.74(s, 1H)(CDCl.sub.3)                      38a H H F H H CH N H N 4 HCl 3450, 2429, 2707, 1.74(m, 2H); 1.86(m, 2H);       2.68(m, 1H); 2.84(m, 1H);                                                                  166-168° C. 2593, 1512, 1437, 3.16(a.c., 3H); 3.53(m,       1H); 3.70(m, 1H); 3.91(m,                                                                   1230, 816, 626 1H); 4.27(t, J=6.7Hz, 2H); 6.12(s, 1H);            7.19(t, J=8.9Hz,                                                                            KBr 2H; 7.50(dd, J=7.2Hz, J'=5.5Hz, 2H); 8.23(s, 1H); 8.93                       (s, 1H); 11.02(b.a., 1H)(DMSO-d.sub.6)                           39a H H F H H CH N H N 4 oil 2944, 2808, 2773, 1.60(m, 2H); 1.97(m,           2H); 2.40-2.70(a.c., 6H); 3.12                                                              1602, 1510, 1273, (m, 2H); 4.22(t, J=6.9Hz, 2H); 5.99(m,          1H); 6.98(m,                                                                                1227, 1161, 1140, 2H); 7.35(m, 2H); 7.95(s, 1H); 8.07(s,          1H)(CDCl.sub.3)                                                                             846, 824, 681                                                                  film                                                               40a H H F H H CCH.sub.3 N CHCHCHCHC 4 oil 2932, 1512, 1456, 1.63(m,           2H); 1.88(m, 2H); 2.42-2.55(a.c., 4H); 2.61                                                1404, 1231, 744 (s, 3H); 2.65(t, J=5.5Hz, 2H); 3.09(m, 2H);        4.14                                                                                       film (t, J=7.3Hz, 2H); 5.97(m, 1H); 6.99(m, 2H); 7.19-7.35                        (a.c., 5H); 7.68(m, 1H)(CDCl.sub.3)                              41a H H F H H N CH CHCHCHCHC 4 oil 2932, 2805, 1511, 1.57(m, 2H);             1.99(m, 2H); 2.42-2.50(a.c., 4H); 2.62                                                     1465, 1230, 1160, (t, J=5.6Hz, 2H); 3.06(m, 2H); 4.42(t,           J=6.9Hz, 2H); 5.95                                                                         825, 752, 741 (m, 1H); 6.97(t, J=8.8Hz, 2H); 7.12(m, 1H);          7.25-7.41                                                                                  film (a.c., 4H); 7.71(d, J=8Hz, 1H); 7.99(s, 1H)(CDCl.sub.3)        42a H H F H H N CCHCHCHCH CH 4 102-103° C. 2941, 1510, 1374,           1.59(quin., J=7.0Hz, 2H); 2.09(quin., J=7.5Hz, 2H);                                        1226, 1162, 806, 2.40-2.50(a.c., 4H); 2.64(t, J=6.2Hz, 2H);        3.10(m, 2H);                                                                               759, 741 4.45(t, J=7.1Hz, 2H); 5.96(m, 1H); 6.98(t, J=8.8Hz,       2H);                                                                                       KBr 7.07(t, J=7.6Hz, 1H); 7.20-7.35(a.c., 3H); 7.63                             (d, J=8.5Hz, 1H); 7.71(d, J=8.6Hz, 1H); 7.90(s, 1H)                                    (CDCl.sub.3)                                               43a H H F H H N CCHCHCHCH N 4 HCl 2574, 2482, 1510, 1.80(m, 2H);              2.11(quin., J=7.2Hz, 2H); 2.69(m, 1H);                                                    208-209° C. 1231, 745 2.83(m, 1H); 3.10-3.20(a.c.,           3H); 3.52(m, 1H); 3.71                                                                     KBr (m, 1H); 3.88(m, 1H); 4.80(t, J=6.3Hz, 2H); 6.11(s,                              1H); 7.19(m, 2H); 7.41(m, 2H); 7.50(m, 2H); 7.91(m,                          (2H); 11.07(b.a., 1H)(DMSO-d.sub.6)                             44a H H F H H N CCHCHCHCH N 4 76-77° C. 2913, 1511, 1470,              1.60(quin., J=7.5Hz, 2H); 2.19(quin., J=8.2Hz, 2H);                                        1380, 1327, 1224, 2.41-2.59(a.c., 4H); 2.64(t, J=5.7Hz, 2H);       3.08(m, 2H);                                                                               1172, 1132, 851, 826, 4.77(t, J=7.0Hz, 2H); 5.95(m, 1H);           6.97(t, J=8.8Hz, 2H);                                                                      757 7.25-7.40(a.c., 4H); 7.85(m, 2H)(CDCl.sub.3)                               KBr                                                                 45a H H F H H N N CHCHCHCHC 4 HCl 2928, 2680, 2573, 1.81(m, 2H);              1.99(m, 2H); 2.67(m, 1H); 2.84(m, 1H);                                                    204-205° C. 2559, 1515, 1454, 3.10-3.20(a.c., 3H);           3.53(m, 1H); 3.72(m, 1H); 3.90                                                             1272, 1242, 1224, (m, 1H); 4.76(t, J=6.9Hz, 2H); 6.12(s,           1H); 7.19                                                                                  1166, 819, 745 (t, J=8.8Hz, 2H); 7.39(t, J=7.6Hz, 1H);             7.45-7.60(a.c.,                                                                            KBr 3H); 7.94(d, J=8.3Hz, 2H); 8.03(d, J=8.3Hz, 2H); 11.04                        (b.a., 1H)(DMSO-d.sub.6)                                         46a H H F H H N N CHCHCHCHC 4 88-90° C. 2939, 1510, 1229,              1.58(quin., J=7.5Hz, 2H); 2.07(quin, J=7.5Hz, 2H);                                         1209, 1164, 744 2.40-2.50(a.c., 4H); 2.61(m, 2H); 3.05(m,          2H); 4.66                                                                                  KBr (t, J=7.0Hz, 2H); 5.95(m, 1H); 6.96(t, J=8.8Hz, 2H);                            7.23-7.38(a.c., 3H); 7.44(m, 1H); 7.52(m, 1H); 8.04                            (d, J=8.3Hz, 1H)(CDCl.sub.3)                                   47a H H Cl H H N CH Cl CH 4 HCl 3068, 2948, 1491, 1.71(m, 2H); 1.80(m,        2H); 2.70(m, 1H); 2.83(m, 1H);                                                             172-173° C. 1445, 1320, 1308, 3.15-330(a.c., 3H);           3.44(m, 1H); 3.72(m, 1H); 3.89(m,                                                           1096, 968, 809, 799 1H); 4.11(t, J=6.5Hz, 2H); 6.20(s, 1H);       7.41(Syst.                                                                                  KBr AB, J.sub.AB =8.8Hz, 2H); 7.48(Syst. AB, J.sub.AB             =8.8Hz, 2H); 7.52                                                                            (s, 1H); 8.04(s, 1H); 10.98(b.a., 1H)(DMSO-d.sub.6)                      48a H H H H H N CH H CH 4 HCl 2955, 2929, 2530, 1.70-190(a.c.,         4H); 2.69(m, 1H); 2.89(m, 1H); 3.10-                                                       180-181° C. 1445, 965, 761, 745 3.20(a.c., 3H);             3.53(m, 1H); 3.70(m, 1H); 3.91(m,                                                           KBr 1H); 4.15(t, J=6.5Hz, 2H); 6.16(m, 1H); 6.23(m, 1H);                           7.28-7.50(a.c., 6H); 7.78(m, 1H); 11.26(b.a., 1H)                                 (DMSO-d.sub.6)                                              49a H H H H H CH N H N 4 HCl 2937, 2370, 1503, 1.74(m, 2H); 1.84(m,           2H); 2.72(m, 1H); 2.87(m, 1H);                                                             122-123° C. 1276, 1142, 774, 755 3.10-3.20(a.c., 3H);       3.54(m, 1H); 3.73(m, 1H); 3.88                                                              KBr (m, 1H); 4.22(t, J=6.6Hz, 2H); 6.15(s, 1H); 7.27-7.70                         (a.c., 3H); 7.47(m, 2H); 7.97(s, 1H); 8.59(s, 1H); 11.20                     (b.a., 1H)(DMSO-d.sub.6)                                          50a H H H H H CPh N H CH 4 HCl 2930, 2554, 1469, 1.62-1.78(a.c., 4H);         2.75(m, 2H); 3.00(m, 2H); 3.25                                                             170-171° C. 1459, 1444, 1278, (m, 2H); 3.69(m, 2H);         4.08(t, J=6.7Hz, 2H); 6.13(s,                                                               1075, 744, 762, 749, 1H); 7.07(s, 1H); 7.24-7.40(a.c., 3H);       7.42-7.52(a.c.,                                                                             732, 711, 702, 690 6H); 7.62(Syst. AB, J.sub.AB =7.6Hz,           2H)(DMSO-d.sub.6)                                                                           KBr                                                                51a H H H H H CH CH H CH 4 HCl 2930, 2482, 1448, 1.60-1.80(a.c., 4H);         2.70(m, 1H); 2.84(m, 1H); 3.08-                                                            197-199° C. 1280, 1090, 732 3.22(a.c., 3H); 3.50(m,         1H); 3.71(m, 1H); 3.86-3.96                                                                 KBr (a.c., 3H); 5.97(t, J=2.1Hz, 2H); 6.16(m, 1H); 6.76                             (t, J=2.1Hz, 2H); 7.25-7.50(a.c., 5H); 10.74(b.a., 1H)                     (DMSO-d.sub.6)                                                    52a H H H H H CH CH H CH 4 58-60° C. 2928, 1498, 1280, 1.58(m,         2H); 1.84(m, 2H); 2.47(t, J=7.5Hz, 2H); 2.58                                                1262, 1137, 1087, (m, 2H): 2.68(m, 2H); 3.13(m, 2H);              3.92(t, J=7.1Hz,                                                                            1060, 747, 723, 691 2H); 6.06(m, 1H); 6.15(t, J=2.2Hz, 2H);       6.67(t, J=2.2Hz,                                                                            KBr 2H); 7.24-7.42(a.c., 5H)(CDCl.sub.3)                           53a H H H H H N CCl CHCHCHCHC 4 oil 2939, 1495, 1467, 1.58(quin.              J=7.6Hz, 2H); 1.99(quin, J=7.6Hz, 2H); 2.47                                                1338, 745 (m, 2H); 2.55(m, 2H); 2.65(m, 2H); 3.10(m, 2H);          4.36                                                                                       film (t, J=7.1Hz, 2H); 6.04(m, 1H); 7.18-7.42(a.c., 8H);           7.67                                                                                        (d, J=7.6Hz, 1H)(CDCl.sub.3)                                       54a H H H H H N CCl CHCHCHCHC 4 HCl 3460, 2940, 2550, 1.80(m, 2H);            1.90(m, 2H); 2.70(m, 1H); 2.87(m, 1H);                                                    164-165° C. 1338, 743 3.07-3.22(a.c., 3H); 3.52(m,           1H); 3.71(m, 1H); 3.87                                                                     KBr (m, 1H); 4.43(t, J=6.6Hz, 2H); 6.14(s, 1H); 7.20-7.52                          (a.c., 7H); 7.65(m, 1H); 7.79(m, 1H); 11.16(b.a., 1H)                          (DMSO-d.sub.6)                                            

BIOLOGICAL TESTS

Binding to The Serotonin Receptor (5-HT_(1A))

A rat hippocampus homogenate is used, a modification of the process ofS. J. Peroutka, J. of Neurochem., 47(2), 529-540 (1986) being followed.³ H!-8-OH-DPAT is used as radioligand and serotonin is used formeasuring the non-specific binding. The incubation time is 15 minutes ata temperature of 37° C. The radioligand bound to the protein isseparated by filtration on glass fiber filters and the radioactivityretained on the filter is determined by liquid scintillation. Theinhibition constants (K_(i), nM) are calculated by non-linear regressionanalysis by using the EBDA/LIGAND program (Munson and Rodbard,Analytical Biochemistry, 107, 220 (1980)).

Binding to the Sigma Receptor

A guinea pig brain (less the cerebellum) homogenate is used, amodification of the process of L. Radesca et al., J. Med. Chem., 34,3058-3065 (1991) being followed. ³ H!-(+)-3-PPP is used as radioligandand haloperidol is used for measuring the non-specific binding. Theincubation time is 120 minutes at a temperature of 25° C. Theradioligand bound to the protein is separated by filtration on glassfiber filters and the radioactivity retained on the filter is determinedby liquid scintillation. The inhibition constants (K_(i), nM) arecalculated by non-linear regression analysis by using the EBDA/LIGANDprogram (Munson and Rodbard, Analytical Biochemistry, 107, 220 (1980)).

                  TABLE III                                                       ______________________________________                                        BINDING                                                                                   Sigma              5-HT.sub.1A                                                Ki     % Des       Ki   % Des                                     Example     (nM)   (10.sup.-6 M)                                                                             (nM) (10.sup.-6 M)                             ______________________________________                                        1           6.6    93                                                         2           15     90                                                         5           6.4    94               12                                        6           4.3    95                                                         1a          46     86          37   94                                        2a                 82               78                                        3a          11     97          56   90                                        4a          11     93          199  72                                        5a          19     96          6.1  97                                        6a                 91          9.0  100                                       7a                 96          0.4  98                                        8a                 97               90                                        9a                 97          4.6  100                                       10a         40     88          1.3  100                                       11a                92               93                                        14a                94               94                                        15a         8.4    94               98                                        16a         17     95               86                                        BMY 14802   733                                                               ______________________________________                                    

The daily dose in human medicine is between 1 milligram and 500milligrams of product, which can be administered in one or a number ofintakes. The compositions are prepared in formulae compatible with themethod of administration used, such as, for example, tablets, dragees,capsules, suppositories, solutions or suspensions. These compositionsare prepared by known processes and they comprise from 1 to 60% byweight of active principle (compound of general formula I) and from 40to 99% by weight of appropriate pharmaceutical vehicle compatible withthe active principle and the physical form of the composition used. Byway of example, the formula of a tablet which contains a product of theinvention is presented.

Example of a formula for a tablet

    ______________________________________                                        Example 11a       5 mg                                                        Lactose           60 mg                                                       Crystalline cellulose                                                                           25 mg                                                       Povidone K 90     5 mg                                                        Pregelatinized starch                                                                           3 mg                                                        Colloidal silicon dioxide                                                                       1 mg                                                        Magnesium stearate                                                                              1 mg                                                        Total weight      100 mg                                                      ______________________________________                                    

We claim:
 1. A method of treating a condition selected from anxiety, psychosis, epilepsy, convulsion, motoricity problems, amnesia and senile dementia comprising administering to a patient in need of such treatment, an effective amount of at least one compound having the formula ##STR19## and its physiologically acceptable salts, wherein R₁, R₂ R₃, which are identical or different, each represent a hydrogen atom, a halogen atom, a linear or branched alkyl radical, an aryl or substituted aryl radical or an alkoxyl radical;A represents a carbon atom and the dotted line represents an additional bond or A represents a carbon atom bonded to a hydroxyl group (C--OH) and the dotted line represents the absence of an additional bond, n can have values ranging from 2 to 6, Z₁ represents a nitrogen atom or a substituted carbon atom which can be represented by C--R Z₂ represents a nitrogen atom or a substituted carbon atom which can be represented by C--R₅, and Z₄ represents a nitrogen atom or a substituted carbon atom which can be represented by C--R₁, wherein all of Z₁, Z₂ Z₄ cannot be a nitrogen atom, where R₄, R₅, R₆ and R₇, which are identical or different, represent a hydrogen atom, a halogen atom, a linear or branched alkyl radical, a hydroxyl radical, an alkoxyl radical, a carboxyl radical, a carboxamide radical, an alkyl carboxylate radical or an aryl or substituted aryl radical.
 2. The method of claim 1 wherein the compound is 4,5-dichloro-2-methyl-1- 4-(4-phenyl-1,2,3,6-tetrahydro-1-pyridyl)butyl!-1H imidazole, 4,5-dichloro-2-methyl-1- 4-(4-phenyl-1,2,3,6-tetrahydro-1-pyridyl)butyl!-1H-imidazole hydrochloride, or 4,5-dichloro-2-methyl-1 4-(4-phenyl-1,2,3,6-tetrahydro-1-pyridyl)butyl!-1H-imidazole dihydrochloride. 